HIV/AIDS & Hepatitis C: Contrasting Pathways in Prevention and Treatment Ronald P. Hattis, MD, MPH...
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Transcript of HIV/AIDS & Hepatitis C: Contrasting Pathways in Prevention and Treatment Ronald P. Hattis, MD, MPH...
HIV/AIDS & Hepatitis HIV/AIDS & Hepatitis C: Contrasting C: Contrasting Pathways in Pathways in
Prevention and Prevention and TreatmentTreatment
Ronald P. Hattis, MD, MPHRonald P. Hattis, MD, MPHBeyond AIDS FoundationBeyond AIDS FoundationUpdated December 2013Updated December 2013
11
Some interesting Some interesting contrasts between contrasts between hepatitis C and HIVhepatitis C and HIV
HEPATITIS CHEPATITIS C 1. Always reportable 1. Always reportable
by name in Californiaby name in California 2. Written consent 2. Written consent
was never needed was never needed for testingfor testing
3. About 3-4 million 3. About 3-4 million infected in USinfected in US
4. Hardly any money 4. Hardly any money for prevention andfor prevention and treatmenttreatment
HIVHIV 1. Not reportable by 1. Not reportable by
name until 2006name until 2006 2. Written consent 2. Written consent
was formerly was formerly needed for testingneeded for testing
3. About 1.1 million 3. About 1.1 million infected in USinfected in US
4. Lots of money for 4. Lots of money for prevention and prevention and treatmenttreatment
22
More interesting More interesting contrasts between contrasts between hepatitis C and HIV, the hepatitis C and HIV, the “Continuum of Care”“Continuum of Care”HEPATITIS C (U.S.)HEPATITIS C (U.S.) 1. 50% tested1. 50% tested 2. 38% in care2. 38% in care 3. 18% treated3. 18% treated 4. 14% sustained 4. 14% sustained
virological virological responseresponse
(estimates based on (estimates based on survey)survey)
HIV (U.S.)HIV (U.S.) 1. 80%1. 80% 2. 62%2. 62% 3. 36% treated3. 36% treated 4. 28% 4. 28%
undetectable viral undetectable viral loadload
(based on studies of (based on studies of CDC data, 2011) CDC data, 2011)
33
How could discrepancies be addressed How could discrepancies be addressed
for better prevention and treatment?for better prevention and treatment? If HIV/AIDS could be treated in a less If HIV/AIDS could be treated in a less
exceptional manner, techniques that have exceptional manner, techniques that have been successful in controlling syphilis and been successful in controlling syphilis and TB could be more easily applied (e.g., TB could be more easily applied (e.g., reporting, partner notification, routine reporting, partner notification, routine screening, and case management to screening, and case management to influence safe behavior)influence safe behavior)
If hepatitis C could achieve attention and If hepatitis C could achieve attention and funding on the scope of HIV/AIDS, control funding on the scope of HIV/AIDS, control and treatment efforts could be more and treatment efforts could be more proportional to the magnitude of the proportional to the magnitude of the problemproblem 44
Interactions between HIV Interactions between HIV and hepatitis Cand hepatitis C
Many drug users with HIV also acquired Many drug users with HIV also acquired hepatitis C through the same means hepatitis C through the same means (needle sharing).(needle sharing).
Since hepatitis C is much more prevalent, Since hepatitis C is much more prevalent, a high proportion of HIV patients also have a high proportion of HIV patients also have hepatitis C, but the proportion of hepatitis hepatitis C, but the proportion of hepatitis C patients with HIV is relatively small.C patients with HIV is relatively small.
HIV promotes hepatitis C progression to HIV promotes hepatitis C progression to cirrhosis, cancer, and liver failure, so that cirrhosis, cancer, and liver failure, so that severe liver disease occurs earlier.severe liver disease occurs earlier.
55
Interactions between HIV Interactions between HIV and hepatitis C, contd.and hepatitis C, contd.
Hepatitis C also makes it harder to treat HIVHepatitis C also makes it harder to treat HIV– Many drugs must be metabolized by the liver. Many drugs must be metabolized by the liver. – Drugs for HIV may further damage the liver.Drugs for HIV may further damage the liver.
Hepatitis C increases mortality by 50% in patients Hepatitis C increases mortality by 50% in patients with AIDS with AIDS http://www.aidsmap.com/Co-infection-with-hepatitis-C-increases-http://www.aidsmap.com/Co-infection-with-hepatitis-C-increases-mortality-risk-by-50-for-patients-with-AIDS/page/2338061/mortality-risk-by-50-for-patients-with-AIDS/page/2338061/
Annual U.S. deaths from hepatitis C now exceed Annual U.S. deaths from hepatitis C now exceed those from HIV/AIDS those from HIV/AIDS http://www.aidsmeds.com/articles/hiv_hcv_deaths_1667_21929.shtml
Treatment recommendations for hepatitis C not Treatment recommendations for hepatitis C not changed by presence of HIV, but more effective in changed by presence of HIV, but more effective in HIV-negative.HIV-negative.
66
Interactions between HIV Interactions between HIV and hepatitis C, contd.and hepatitis C, contd.
HIV patients also infected with HIV patients also infected with hepatitis C are not as able to hepatitis C are not as able to suppress hepatitis C, and have suppress hepatitis C, and have larger numbers of hepatitis C larger numbers of hepatitis C viruses in their plasma and livers.viruses in their plasma and livers.
Hepatitis C may be more infectious Hepatitis C may be more infectious sexually and from mother to infant sexually and from mother to infant in HIV co-infected patients.in HIV co-infected patients.
77
Comparing the viruses: HIV and Comparing the viruses: HIV and HCVHCV
Both HIV and HCV are RNA virusesBoth HIV and HCV are RNA viruses– do most of their damage through insidious, do most of their damage through insidious,
chronic infection after long asymptomatic periods.chronic infection after long asymptomatic periods.
Both HIV and HCV mutate frequentlyBoth HIV and HCV mutate frequently– causing enough variability in surface proteins to causing enough variability in surface proteins to
evade antibody attacksevade antibody attacks– antibodies are a marker for infection rather than antibodies are a marker for infection rather than
evidence of immunity.evidence of immunity.
For hepatitis C, most transmission is by For hepatitis C, most transmission is by needle and only minimally by sexneedle and only minimally by sex
For HIV, most transmission is by sex and For HIV, most transmission is by sex and secondarily by needle.secondarily by needle.
88
Comparing the HIV and Comparing the HIV and hepatitis C epidemics in the hepatitis C epidemics in the
U.S.U.S. Incidence of hepatitis C in the U.S. is past its Incidence of hepatitis C in the U.S. is past its
peak, but the impact of eventual cirrhosis, liver peak, but the impact of eventual cirrhosis, liver failure, and liver cancer from already-infected failure, and liver cancer from already-infected persons will be immense.persons will be immense.
HIV incidence has been stable, but prevalence is HIV incidence has been stable, but prevalence is increasing, in part because of longer life spansincreasing, in part because of longer life spans
Supposing hepatitis C were only 20% as deadly Supposing hepatitis C were only 20% as deadly as HIV but the prevalence is 5 times higher, how as HIV but the prevalence is 5 times higher, how will the ultimate mortality compare?will the ultimate mortality compare?– Actual mortality will depend on effectiveness of future Actual mortality will depend on effectiveness of future
treatments as well as on courses of the epidemicstreatments as well as on courses of the epidemics99
HIV at its Worst: HIV prevalence in 5 countries in sub-Saharan Africa before
treatment introduction (lower now)Source: UNAIDS 2000
Update South Botswana Namibia Lesotho
Swaziland Africa
Population (000s) 39,900 1,597 1,695 2,108980
Population 5-49 (000s) 20,982 786 795 1,000468
% of Total Popn. w/HIV 10.50% 18.20% 9.40% 11.40% 13.30%
HIV Infected People (000s) 4,200 290 160 240130
Adult Prev. Rate of HIV 20.00% 35.80% 19.50% 23.60%25.30%
% of HIV in Females 54.80% 51.20% 53.10% 54.20%51.50%
Pregnant Women HIV Prev. 19.20% 43.00% 25.90% N/A30.30%
AIDS Orphans (Living 370,952 54,943 53,023 29,469 10,705
1010
OK, that’s Africa; how about OK, that’s Africa; how about the U.S. - Is HIV under control the U.S. - Is HIV under control here?here? Estimated 45-50,000 new cases Estimated 45-50,000 new cases
continue to occur yearlycontinue to occur yearly– Actually represents overlap of Actually represents overlap of
epidemic course in multiple sub-epidemic course in multiple sub-population groupspopulation groups Increasing in young gay malesIncreasing in young gay males Decreasing in black females and ? Decreasing in black females and ?
injection drug usersinjection drug users Recent resurgence of syphilis Recent resurgence of syphilis
among and accompanied by HIV among and accompanied by HIV infections among young gay infections among young gay males.males.
1111
Other ominous HIV trends in Other ominous HIV trends in U.S.U.S.
Published reports show infected Published reports show infected men who are told their HIV viral men who are told their HIV viral loads are low or undetectable loads are low or undetectable sometimes assume they are not sometimes assume they are not infectious, and reduce safe infectious, and reduce safe behavior.behavior.
Increases in “barebacking” and Increases in “barebacking” and “bug-chasing” (intentionally “bug-chasing” (intentionally becoming infected) have been becoming infected) have been reported.reported.
50% of new HIV cases are 50% of new HIV cases are occurring in African-Americansoccurring in African-Americans..
1212
Prevalence of HCV Prevalence of HCV (Hepatitis C Virus) Antibody (Hepatitis C Virus) Antibody
in U.S.in U.S. 1.8% of US population, ~ 4,000,000 (4 1.8% of US population, ~ 4,000,000 (4 times the prevalence of HIV)times the prevalence of HIV)– But up to 30% prevalence in jails and prisons But up to 30% prevalence in jails and prisons
(10 times the prevalence of HIV)(10 times the prevalence of HIV)
1% of population HCV RNA (+), ~ 1% of population HCV RNA (+), ~ 2,700,0002,700,000RaceRace– WhiteWhite 1.5% 1.5%– BlackBlack 3.2% 3.2%– Mexican 2.1%Mexican 2.1%
Highest prevalence in “baby boomers” Highest prevalence in “baby boomers” born 1945-65born 1945-65
CDC. MMWR. 1998;47(RR-19):1-39. 1313
Decline among Decline among transfusion recipientstransfusion recipients
Decline among Decline among injection-drug usersinjection-drug users
YearYear
55
1010
1515
2020
00
8282 8484 8585 8686 8787 8888 8989 9090 9191 9292 93938383 9494 9595 9696
Cases per Cases per 100,000100,000
Centers for Disease Control and Prevention. Unpublished data.Centers for Disease Control and Prevention. Unpublished data.
Estimated Incidence,Estimated Incidence,United States, 1982-1996United States, 1982-1996
Acute Hepatitis CAcute Hepatitis C
HIV Prevention MeasuresHIV Prevention Measures
(type 1)
A cohort of “baby boomers” born 1945-65 have highest A cohort of “baby boomers” born 1945-65 have highest prevalence prevalence 1414
Sources of hepatitis CSources of hepatitis C
1515
AcquisitionAcquisition and Course Of and Course Of Hepatitis CHepatitis C
Genotype commonest in the US (type 1) Genotype commonest in the US (type 1) unfortunately unfortunately worstworst in prognosis and in prognosis and poorest in responsiveness to treatmentpoorest in responsiveness to treatment- Treatment for this type requires 3 drugsTreatment for this type requires 3 drugs
- Approximately 85-90% of infected persons Approximately 85-90% of infected persons become chronically infected become chronically infected – Remainder of infections resolve clinicallyRemainder of infections resolve clinically– Unknown if virus is ever totally eradicatedUnknown if virus is ever totally eradicated
Course of Hepatitis C Course of Hepatitis C variablevariable– Severity of illness ranges from transient, self Severity of illness ranges from transient, self
limited and asymptomatic infection to a limited and asymptomatic infection to a chronic, progressive liver diseasechronic, progressive liver disease May lead ultimately (usually >20 yrs.) to cirrhosis, May lead ultimately (usually >20 yrs.) to cirrhosis,
HCC, or liver failureHCC, or liver failure1616
The escalating cost of hepatitis Chepatitis C
As with HIV, acute infection causes As with HIV, acute infection causes minimal mortality and patients are minimal mortality and patients are usually asymptomatic for yearsusually asymptomatic for years
Serious disease usually takes 20+ years, Serious disease usually takes 20+ years, vs. 10+ for HIVvs. 10+ for HIV
Late liver disease will increase as Late liver disease will increase as infections matureinfections mature– CirrhosisCirrhosis– Hepatocellular carcinoma (rarely without Hepatocellular carcinoma (rarely without
cirrhosis)cirrhosis)– Liver failureLiver failure
Hepatitis C already leading cause of liver Hepatitis C already leading cause of liver transplantstransplants
1717
Prevention considerationsPrevention considerations
HIV and hepatitis C have no cures or HIV and hepatitis C have no cures or vaccines vaccines
To prevent transmission, infected persons To prevent transmission, infected persons must reduce partners and likelihood of must reduce partners and likelihood of infecting each partner infecting each partner
Usually requires behavior change; Usually requires behavior change; sometimes, cultural change in an entire sometimes, cultural change in an entire communitycommunity
Many people will change behavior if they know Many people will change behavior if they know they are infected, but both infections may be they are infected, but both infections may be asymptomatic for yearsasymptomatic for years– People may not know they have been exposed, let People may not know they have been exposed, let
alone infectedalone infected
1818
Prevention considerations, Prevention considerations, contd.contd.
Widespread combined screening and Widespread combined screening and partner notification programs for both partner notification programs for both diseases therefore would seem sensiblediseases therefore would seem sensible
– Mass screening for hepatitis C was not Mass screening for hepatitis C was not funded till 2013funded till 2013
As of 2013, insurance must cover one-time As of 2013, insurance must cover one-time hepatitis C screen for birth cohort 1945-65 hepatitis C screen for birth cohort 1945-65
– Some of the funded screening for HIV is Some of the funded screening for HIV is anonymous, and most has been limited to anonymous, and most has been limited to HIV aloneHIV alone
– Partner tracing and notification never Partner tracing and notification never implemented for hepatitis C, insufficiently implemented for hepatitis C, insufficiently funded in many locations for HIVfunded in many locations for HIV
1919
The concept of The concept of reproductive rate of a reproductive rate of a disease agentdisease agent
To gradually bring a communicable disease To gradually bring a communicable disease into control, the reproductive rate of the into control, the reproductive rate of the infectious agent (infectious agent (RRoo) must be less than one. ) must be less than one.
RRoo is the number of new cases resulting from is the number of new cases resulting from each case. each case. RRoo == (average transmissions per (average transmissions per exposure) x (exposures/partner) x (partners exposure) x (exposures/partner) x (partners exposed/time) x (length of time patient is exposed/time) x (length of time patient is infectious, lifelong for HIV).infectious, lifelong for HIV).
If this number is greater than one, the If this number is greater than one, the disease will continue to increase disease will continue to increase exponentially.exponentially.
2020
Reproductive rate, contd. Reproductive rate, contd. Ways to reduce RWays to reduce Ro o thereforetherefore include:include:
– Reducing infectiousness of sex or drug abuse, Reducing infectiousness of sex or drug abuse, by using condoms, or clean needles (“harm by using condoms, or clean needles (“harm reduction”)reduction”)
– Eliminating the behavior that causes exposure, Eliminating the behavior that causes exposure, by abstinence, or non-use of injecting drugs by abstinence, or non-use of injecting drugs (exposure prevention, the truest primary (exposure prevention, the truest primary prevention and the topic for another talk)prevention and the topic for another talk)
– Reducing number of persons exposed, by Reducing number of persons exposed, by maintaining only monogamous relationships, or maintaining only monogamous relationships, or non-sharing of needlesnon-sharing of needles
If the average infected person does not If the average infected person does not even know s/he is infected until having even know s/he is infected until having already transmitted the disease, it is already transmitted the disease, it is difficult to explain how difficult to explain how RRoo can be <1 and can be <1 and current prevention strategy can contain current prevention strategy can contain the epidemic.the epidemic.
2121
What else is needed to control What else is needed to control transmission of HIV and transmission of HIV and
hepatitis C?hepatitis C? Communicable diseases are ordinarily Communicable diseases are ordinarily
controlled at the source (the infected controlled at the source (the infected person)person)
Direct outreach infected persons Direct outreach infected persons (“prevention with positives”) has not been (“prevention with positives”) has not been linked to case reporting for either HIV and linked to case reporting for either HIV and hepatitis C (nor for hepatitis B)hepatitis C (nor for hepatitis B)
In the case of HIV, the excuse should not be In the case of HIV, the excuse should not be lack of money, but for hepatitis C, it may belack of money, but for hepatitis C, it may be
Antiviral treatment greatly reduces HIV Antiviral treatment greatly reduces HIV transmission and might do same for transmission and might do same for hepatitis hepatitis
2222
““Prevention with Prevention with positives”positives”
““Prevention case management” can assist Prevention case management” can assist infected patients to avoid infecting othersinfected patients to avoid infecting others
– This can involve treatment adherence, This can involve treatment adherence, encouraging a sense of responsibility not to infect encouraging a sense of responsibility not to infect others, and help with techniques for behavior others, and help with techniques for behavior changechange
Partner services (incl. notification) can Partner services (incl. notification) can influence earlier reduction in transmission-influence earlier reduction in transmission-prone behavior of persons already infected, prone behavior of persons already infected, help exposed but not yet infected persons to help exposed but not yet infected persons to remain uninfected, and lead to earlier remain uninfected, and lead to earlier treatment treatment
These services are not routine in most parts These services are not routine in most parts of California or other places in U.S.of California or other places in U.S.
2323
The Uganda Model: “ABC”The Uganda Model: “ABC” A program that seems to have been A program that seems to have been
responsible for reduction of unsafe responsible for reduction of unsafe behavior and HIV prevalence in Uganda is behavior and HIV prevalence in Uganda is known as “ABC.” This became a known as “ABC.” This became a centerpiece of the Global AIDS Bill.centerpiece of the Global AIDS Bill.
AA = Abstain from sex if possible = Abstain from sex if possible
BB = Be faithful if already involved in a sexual = Be faithful if already involved in a sexual relationshiprelationship
CC = Condoms should be used if A and B are not = Condoms should be used if A and B are not possible.possible.
No current equivalent for needle transmission No current equivalent for needle transmission (most common for hepatitis C)(most common for hepatitis C)
2424
Objectives of Beyond Objectives of Beyond AIDS and allied groupsAIDS and allied groups
Eliminate barriers to applying the most Eliminate barriers to applying the most effective possible prevention techniques for effective possible prevention techniques for HIV. e.g.:HIV. e.g.:– Confidential reporting by name (battle won 2006)Confidential reporting by name (battle won 2006)– Contact tracing, partner notification, and Contact tracing, partner notification, and
prevention case managementprevention case management– Routine and universal screeningRoutine and universal screening– Promotion of cultural changes to avoid exposurePromotion of cultural changes to avoid exposure
Not just depending on reducing the harm caused by Not just depending on reducing the harm caused by exposureexposure
– Devoting resources to diseases in proportion to Devoting resources to diseases in proportion to their importance as public health problemstheir importance as public health problems 2525
Objectives of Beyond Objectives of Beyond AIDS and allied groups, AIDS and allied groups, contd.contd. Eventually, reverse the course of Eventually, reverse the course of
the global HIV pandemic through the global HIV pandemic through sound public health policysound public health policy
Direct attention and resources to Direct attention and resources to other neglected public health other neglected public health priorities, such as hepatitis Cpriorities, such as hepatitis C
Prioritize prevention of transmissionPrioritize prevention of transmission
2626
The non-routine nature of The non-routine nature of HIV testingHIV testing Anonymous testing offered, on assumption Anonymous testing offered, on assumption
that stigma of HIV will deter confidential that stigma of HIV will deter confidential testingtesting– Also, originally, to avoid use of blood bank Also, originally, to avoid use of blood bank
donations to find out HIV status donations to find out HIV status
Pre-test counseling was encouraged (and Pre-test counseling was encouraged (and required by law or for funding) until 2006 required by law or for funding) until 2006 CDC guidelines changedCDC guidelines changed– Still required in California as of 2013Still required in California as of 2013
Written consent required by most states Written consent required by most states until 2006 CDC guidelines changeduntil 2006 CDC guidelines changed– Only required in Nebraska, Oklahoma as of 2013Only required in Nebraska, Oklahoma as of 2013
2727
The non-routine nature of The non-routine nature of HIV testing, contd.HIV testing, contd. HIV testing historically has often been HIV testing historically has often been
deferred in medical settings due to time and deferred in medical settings due to time and skill requirements of counselingskill requirements of counseling
HIV testing has not been included in routine HIV testing has not been included in routine panels, including for pregnant women in panels, including for pregnant women in CaliforniaCalifornia
Perception of many patients is that HIV Perception of many patients is that HIV testing is not routine; some may actually be testing is not routine; some may actually be deterred by counseling deterred by counseling
Unique penalties for unauthorized disclosure Unique penalties for unauthorized disclosure of resultsof results
2828
HIV testing: new HIV testing: new technologytechnology
There are now rapid tests, oral and urine tests, There are now rapid tests, oral and urine tests, and home collection kits to mail specimens to and home collection kits to mail specimens to lablab– No home tests to perform yourself…yetNo home tests to perform yourself…yet
November 7, 2002: OraQuick Rapid HIV-1 November 7, 2002: OraQuick Rapid HIV-1 bloodblood test licensed by FDA test licensed by FDA – 20-minute simple fingerstick test20-minute simple fingerstick test– HIV-1/2 version approved March 19, 2004HIV-1/2 version approved March 19, 2004– Approved for clinical laboratoriesApproved for clinical laboratories
Waived CLIA testing approved January 2003 Waived CLIA testing approved January 2003 (apparently for HIV-1(apparently for HIV-1
– Does not include confirmatory testingDoes not include confirmatory testing Can keep specimen for confirmatory Western BlotCan keep specimen for confirmatory Western Blot
2929
HIV testing: new HIV testing: new technology, contd.technology, contd.
March 26, 2004: OraQuick Advance, a Rapid March 26, 2004: OraQuick Advance, a Rapid HIV- 1/2 test approved for HIV- 1/2 test approved for oral mucosal oral mucosal fluidsfluids (not actually saliva) (not actually saliva)– First approved rapid test not requiring bloodFirst approved rapid test not requiring blood
Estimated cost to public health clinics $8/testEstimated cost to public health clinics $8/test http://www.fda.gov/bbs/topics/news/2004/NEW01042.html http://www.medicineonline.com/reference/Health/http://www.medicineonline.com/reference/Health/
Conditions_and_Diseases/Immune_Disorders/Conditions_and_Diseases/Immune_Disorders/Immune_Deficiency/AIDS/info/Rapid-Oral-HIV-Test/Immune_Deficiency/AIDS/info/Rapid-Oral-HIV-Test/
– Oral Western Blot test also approved for Oral Western Blot test also approved for confirmationconfirmation
– CLIA waiver approved June 25, 2004CLIA waiver approved June 25, 2004 http://www.hhs.gov/news/press/2004pres/20040625b.htmlhttp://www.hhs.gov/news/press/2004pres/20040625b.html
– Urine test exists, but not popularUrine test exists, but not popular– Future: Home testing? Pre-date test kits for two?Future: Home testing? Pre-date test kits for two?
3030
HIV testing: new HIV testing: new technology, contd.technology, contd.
What is the difference What is the difference between salivabetween salivaand mucosal transudate?and mucosal transudate?
Oral mucosal transudate Oral mucosal transudate has high concentrations has high concentrations of IgG; saliva has of IgG; saliva has practically none. Oral practically none. Oral mucosal transudate mucosal transudate comes from thecomes from thetissues of the cheek and tissues of the cheek and gum; saliva comes from gum; saliva comes from the salivarythe salivaryglands.glands.
– Information from OraSure Information from OraSure
The OraSure systemdraws HIV antibodies out of the tissues between the cheek and gum. The virus itself is rarely ever found in oral fluid.
This sample, calledmucosal transudate,contains far fewercontaminants thantypically found insaliva.
3131
HIV testing: new HIV testing: new technology, contd.technology, contd.
http://www.freedomantiviral.com/
3232
HIV testing: new HIV testing: new technology, contd.technology, contd.
3333
HIV testing: new HIV testing: new technology, contd.technology, contd.
3434
HIV testing: signs of HIV testing: signs of changechange Fall 2002: CDC leadership Fall 2002: CDC leadership
expresses increasing concernexpresses increasing concern– Estimated 200 to 250 thousand Estimated 200 to 250 thousand
Americans with HIV do not know Americans with HIV do not know their statustheir status Approximately 25%Approximately 25%
– 40,000 new infections/year40,000 new infections/year Despite over 20 years of prevention Despite over 20 years of prevention
efforts.efforts. 3535
HIV testing: signs of HIV testing: signs of change, contd.change, contd. April 18, 2003 (MMWR): CDC recommends:April 18, 2003 (MMWR): CDC recommends:
– Unlinking HIV counseling from testingUnlinking HIV counseling from testing Both still supported but counseling not a prerequisite Both still supported but counseling not a prerequisite
– Making testing routine in medical and other Making testing routine in medical and other settings.settings.
2003: CDC also informally recommending 2003: CDC also informally recommending “opt-out” prenatal testing“opt-out” prenatal testing– Requires active refusal rather than active Requires active refusal rather than active
written consentwritten consent– Not proposed for other settings at this timeNot proposed for other settings at this time
3636
HIV testing: signs of HIV testing: signs of change, contd.change, contd.
September 22, 2006:September 22, 2006: CDC releases revised CDC releases revised recommendations on HIV testing of adults, recommendations on HIV testing of adults, adolescents, pregnant women in health care adolescents, pregnant women in health care settingssettings– Test routinely in all health care settingsTest routinely in all health care settings
At least annually if high riskAt least annually if high risk– No pre-test prevention counselingNo pre-test prevention counseling– No written consent (the new wrinkle)No written consent (the new wrinkle)
BUT still required by law in CaliforniaBUT still required by law in California ““General consent for medical care” adequate General consent for medical care” adequate BUT also states that patient should be notified first and BUT also states that patient should be notified first and
may refuse (“opt-out” screeningmay refuse (“opt-out” screening– Prenatally, in routine panel (but also “opt-out” Prenatally, in routine panel (but also “opt-out”
screening)screening) Retest in third trimester if high local rate of HIV in Retest in third trimester if high local rate of HIV in
pregnancy pregnancy
3737
Prevention of HIV transmission to Prevention of HIV transmission to babies: “routine & universal” babies: “routine & universal” prenatal testing followed by prenatal testing followed by
medicationmedication 1994: ACTG (AIDS Clinical Trials Group) Protocol 1994: ACTG (AIDS Clinical Trials Group) Protocol
076 study using monotherapy076 study using monotherapy– Zidovudine (AZT) can reduce HIV in babies of infected Zidovudine (AZT) can reduce HIV in babies of infected
women by two-thirdswomen by two-thirds
1998: Institute of Medicine report1998: Institute of Medicine report– Advocates routine and universal prenatal testingAdvocates routine and universal prenatal testing– Notes that counseling can be a barrier Notes that counseling can be a barrier
2001: PACTG (Pediatric AIDS Clinical Trials Group) 2001: PACTG (Pediatric AIDS Clinical Trials Group) Protocol 316Protocol 316– Rate of newborn infection can be reduced from over Rate of newborn infection can be reduced from over
20% to about 1.5% with combination therapy 20% to about 1.5% with combination therapy – More recent studies reduced to near zeroMore recent studies reduced to near zero 3838
The struggle to make prenatal The struggle to make prenatal HIV testing more routine HIV testing more routine
in California (3 Beyond AIDS in California (3 Beyond AIDS bills)bills)
2003: AB 16762003: AB 1676 (John Dutra), similar to two (John Dutra), similar to two previous unsuccessful bills, became lawprevious unsuccessful bills, became law– Pamphlet; simple signature for test Pamphlet; simple signature for test
acceptanceacceptance– Still no “opt-out” testing in California, and Still no “opt-out” testing in California, and
written acceptance neededwritten acceptance needed– Bill will make it easier to combine HIV Bill will make it easier to combine HIV
testing with other routine prenatal teststesting with other routine prenatal tests– Women who miss prenatal testing must be Women who miss prenatal testing must be
asked to accept test during labor/deliveryasked to accept test during labor/delivery3939
New treatment trends for New treatment trends for HIVHIV
Since 1996, treatment based on “cocktail” Since 1996, treatment based on “cocktail” of 3 or more drugs, known as HAART (highly of 3 or more drugs, known as HAART (highly active anti-retroviral therapy)active anti-retroviral therapy)
A typical regimen A typical regimen – 2 “NRTIs,” (nucleoside or nucleotide reverse 2 “NRTIs,” (nucleoside or nucleotide reverse
transcriptor inhibitors) combined with one of the transcriptor inhibitors) combined with one of the following:following:– protease inhibitor protease inhibitor – ““NNRTI” (non-nucleoside reverse transcriptase NNRTI” (non-nucleoside reverse transcriptase
inhibitor)inhibitor)– More recently: Integrase inhibitor or entry More recently: Integrase inhibitor or entry
inhibitorinhibitor
4040
New treatment trends for New treatment trends for HIV, contd.HIV, contd.
Earlier regimens involved complex Earlier regimens involved complex dosages up to 5 times during daydosages up to 5 times during day– Multiple pills, some with food, some without Multiple pills, some with food, some without
foodfood Protease inhibitors are combined Protease inhibitors are combined
with ritonavir (a member of same with ritonavir (a member of same group) to boost blood levelsgroup) to boost blood levels
Once daily treatment an Once daily treatment an advantageadvantage– Can increase complianceCan increase compliance– MightMight slow development of resistanceslow development of resistance
4141
New treatment trends for New treatment trends for HIV, contd.HIV, contd.
Once/day drugs now availableOnce/day drugs now available– NRTI’s (Nucleoside and nucleotide reverse NRTI’s (Nucleoside and nucleotide reverse
transcriptase inhibitors):transcriptase inhibitors):– Videx EC (didanosine/ddI, long-acting capsule)Videx EC (didanosine/ddI, long-acting capsule)– Epivir (lamivudine/3TC)Epivir (lamivudine/3TC)– Emtriva (emtricitabine, similar to lamivudine)Emtriva (emtricitabine, similar to lamivudine)– Viread (tenofovir)Viread (tenofovir)
– NNRTI (Non-nucleoside reverse transcriptase NNRTI (Non-nucleoside reverse transcriptase inhibitor):inhibitor):
– Sustiva (efavirenz)Sustiva (efavirenz)– Complera (rilpivirine)Complera (rilpivirine)
– PI (Protease inhibitor):PI (Protease inhibitor):– Reyataz (atazanavir)Reyataz (atazanavir)– Prezista (darunavir) if treatment-naïvePrezista (darunavir) if treatment-naïve
– Entry inhibitorEntry inhibitor– Selzentry (maraviroc)Selzentry (maraviroc)
4242
New treatment trends for New treatment trends for HIV, contd.HIV, contd.
Combination pillsCombination pills– Reduce resistance due to noncomplianceReduce resistance due to noncompliance
Strategy previously utilized for TBStrategy previously utilized for TB
– One pill twice/day combo pillOne pill twice/day combo pill Combivir (zidovudine + lamivudine)Combivir (zidovudine + lamivudine)
– One pill once/day combo pills One pill once/day combo pills (those (those highlighted are complete therapy in 1 pill/d)highlighted are complete therapy in 1 pill/d)
Epzicom (abacavir + lamivudine)Epzicom (abacavir + lamivudine) Truvada (emtricitabine + tenofovir)Truvada (emtricitabine + tenofovir) Atripla (emtricitabine + tenofovir + efavirenz)Atripla (emtricitabine + tenofovir + efavirenz) Complera (emtracitabine + tenofovir + rilpivirineComplera (emtracitabine + tenofovir + rilpivirine Stribild (4 components)Stribild (4 components)
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New treatment trends for New treatment trends for HIV, contd.HIV, contd.
1996-2000: First concept for use of 1996-2000: First concept for use of highly effective drug combinations was highly effective drug combinations was to “hit early, hit hard” to “hit early, hit hard”
2001-2011: onset of treatment was 2001-2011: onset of treatment was delayed till CD4 count decreased delayed till CD4 count decreased (<350, still used internationally; (<350, still used internationally; later <500)later <500)– This change was due to high rate of side This change was due to high rate of side
effects of early drugs and worry about effects of early drugs and worry about developing resistancedeveloping resistance
– During years of infection before treatment During years of infection before treatment criteria were met, most transmission criteria were met, most transmission occurredoccurred
– What was good for public health was not yet What was good for public health was not yet known to also be good for the patient known to also be good for the patient
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New treatment trends New treatment trends for HIV, contd.for HIV, contd.
2012: Treatment guidelines (U.S. 2012: Treatment guidelines (U.S. only) reverted to “hitting early”only) reverted to “hitting early”– Early and continuous treatment Early and continuous treatment
found beneficial to patient outcomesfound beneficial to patient outcomes– Suppression of viral load found 96% Suppression of viral load found 96%
effective in preventing transmissioneffective in preventing transmission– Individual treatment strategy and Individual treatment strategy and
public health strategy now alignedpublic health strategy now aligned
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Treatment trends for Treatment trends for hepatitis Chepatitis C
Former Treatment of hepatitis CFormer Treatment of hepatitis C– Short-acting interferons requiring 3 times Short-acting interferons requiring 3 times
a week (TIW) shotsa week (TIW) shots– Oral ribavirin daily (sold together in Oral ribavirin daily (sold together in
RebetronRebetron®®)) Interferon Interferon alpha-2aalpha-2a (Roferon-A®): 3 MU TIW (Roferon-A®): 3 MU TIW
Interferon Interferon alpha-2balpha-2b (Intron-A®) 3 MU TIW (Intron-A®) 3 MU TIW
Alfacon-1 (Infergen®):Alfacon-1 (Infergen®): 9 9 g TIWg TIW
IFN alpha-2b + Ribavirin (Rebetron®)IFN alpha-2b + Ribavirin (Rebetron®)
3 MU TIW3 MU TIW Pt weight Pt weight ≤ ≤ 75kg: 1000mg75kg: 1000mg
Pt weight > 75kg: 1200mgPt weight > 75kg: 1200mg
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Current treatment: longer acting Current treatment: longer acting “pegylated” interferons, weekly “pegylated” interferons, weekly
shotsshots Only the interferon has changedOnly the interferon has changed
– Now long-acting, inject only once/weekNow long-acting, inject only once/week– Still accompany with daily oral ribavirinStill accompany with daily oral ribavirin
First product:First product:– 12 kD12 kD Peginterferon alpha 2b (PegIntron®) 1.5 Peginterferon alpha 2b (PegIntron®) 1.5
mg/kg injection + Ribavirin 800 mg/day orallymg/kg injection + Ribavirin 800 mg/day orally– Regimen that received FDA approval– Higher Ribavirin doses NOT prospectively
studied nor FDA approved
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Current treatment for hepatitis C, Current treatment for hepatitis C, contd. – latest product contd. – latest product pairpair
40 kD40 kD Peginterferon alpha 2a Peginterferon alpha 2a (Pegasys®) (Pegasys®)
– 180 mcg sq weekly180 mcg sq weekly
+ Ribavirin (Copegus®)+ Ribavirin (Copegus®)≤≤ 75kg, 1000mg/d75kg, 1000mg/d
>75 kg, 1200mg/d>75 kg, 1200mg/d
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Current treatment for Current treatment for hepatitis C, contd. – hepatitis C, contd. – New drugs New drugs as additivesas additives Add a third drug to pegylated interferon Add a third drug to pegylated interferon
and ribavirin for genotype 1and ribavirin for genotype 1– Ages 18 and overAges 18 and over– Bocepravir (Victrelis, approved 5/13/11): 800 Bocepravir (Victrelis, approved 5/13/11): 800
mg tid (q 7-9 hrs) with food, add from wk 4 to mg tid (q 7-9 hrs) with food, add from wk 4 to wk 28 of interferon-ribavirin treatmentwk 28 of interferon-ribavirin treatment
Duration depends on viral RNA monitoringDuration depends on viral RNA monitoring
– Telaprevir (Incivek, approved 5/23/11): 750 mg Telaprevir (Incivek, approved 5/23/11): 750 mg tid (q 7-9 hrs) with food, 1tid (q 7-9 hrs) with food, 1stst 12 wks of treatment 12 wks of treatment
Follow with only 12 more weeks of other 2 drugsFollow with only 12 more weeks of other 2 drugs
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Coming treatment for Coming treatment for hepatitis Chepatitis C Oral drug combinations, IFN and Oral drug combinations, IFN and
ribavirin-free, are eagerly awaited by ribavirin-free, are eagerly awaited by patients and providerspatients and providers
26 drugs being studied, several 26 drugs being studied, several promising drugs in pipeline, 2 approvedpromising drugs in pipeline, 2 approved– Simepravir (Olysio) approved 11/25/13Simepravir (Olysio) approved 11/25/13– Sofosbuvir (Sovaldi) approved 12/6/13Sofosbuvir (Sovaldi) approved 12/6/13– Both once/day; not yet approved for HIV-Both once/day; not yet approved for HIV-
coinfection or for use without interferon coinfection or for use without interferon
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Treatment problemsTreatment problems
All current treatments for both HIV All current treatments for both HIV and hepatitis C are very expensive and hepatitis C are very expensive and have significant toxicityand have significant toxicity
– Antiretroviral drugs cause GI side effects, Antiretroviral drugs cause GI side effects, anemia, rash, fat redistribution anemia, rash, fat redistribution (lipodystrophy), pancreatitis, neuropathy, (lipodystrophy), pancreatitis, neuropathy, hyperlipidemia, even diabetes hyperlipidemia, even diabetes
Sometimes hard to tell which drug is responsible, Sometimes hard to tell which drug is responsible, because used together and HIV alone can cause because used together and HIV alone can cause some of these effectssome of these effects
– Interferon causes flu-like symptoms, Interferon causes flu-like symptoms, neutropenia, thyroid problems, depression, neutropenia, thyroid problems, depression, even suicide; ribavirin causes hemolytic even suicide; ribavirin causes hemolytic anemia and birth defects requiring anemia and birth defects requiring 2 2 methodsmethods of contraception of contraception
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Treatment problems, Treatment problems, contd.contd.
Drugs are needed that are active Drugs are needed that are active against against bothboth HIV and hepatitis C HIV and hepatitis C
– Lamivudine and tenofovir are active Lamivudine and tenofovir are active against both HIV and hepatitis B (so is against both HIV and hepatitis B (so is adefovir, though withdrawn for HIV), but adefovir, though withdrawn for HIV), but no drugs currently help both HIV and no drugs currently help both HIV and hepatitis C.hepatitis C.
– Protease inhibitors, a class in which some Protease inhibitors, a class in which some drugs work for HIV, are now being applied drugs work for HIV, are now being applied for hepatitis C.for hepatitis C.
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Initiatives by private industryInitiatives by private industry
In Africa, pharmaceutical companies In Africa, pharmaceutical companies (stung by criticism for high drug costs) (stung by criticism for high drug costs) collaborating with NGOs (non-collaborating with NGOs (non-governmental organizations) to fund governmental organizations) to fund programs for treatmentprograms for treatment
Pharmaceutical companies reducing prices Pharmaceutical companies reducing prices on drugs for third worldon drugs for third world– Waiving patents to permit local manufacture of Waiving patents to permit local manufacture of
genericsgenerics
In absence of adequate funding for In absence of adequate funding for hepatitis C prevention, pharmaceutical hepatitis C prevention, pharmaceutical companies (e.g., Schering, Roche) have companies (e.g., Schering, Roche) have been a key source of educational materialsbeen a key source of educational materials
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Conclusions:Conclusions:
HIV and hepatitis C are both difficult to HIV and hepatitis C are both difficult to control and difficult to treatcontrol and difficult to treat– Neither is curable and neither has a vaccineNeither is curable and neither has a vaccine– Both are immense public health problems.Both are immense public health problems.
Public health efforts are hampered byPublic health efforts are hampered by– Political restrictions (especially for HIV)Political restrictions (especially for HIV)– Lack of funding (especially for hepatitis C)Lack of funding (especially for hepatitis C)
New strategic approaches and new New strategic approaches and new treatment strategies have recently been treatment strategies have recently been developed which are expected to benefit developed which are expected to benefit patients and reduce transmissionpatients and reduce transmission
Both diseases need a “continuum of Both diseases need a “continuum of care” to detect and treat infected care” to detect and treat infected personspersons
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